Prophylactic application of vaginal lactic acid bacteria against urogenital pathogens and its prospective use in sanitary suppositories.

Beneficial and pathogenic microbes coexist in the vaginal canal, where a diminishing population of lactic acid bacteria may cause recurring urogenital infections. Probiotic bacteria Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus vaginalis, and pathogenic microbes Enterococcus faecalis, Enterobacter cloacae, Shigella sp., Staphylococcus epidermidis, and Escherichia fergusonii were isolated from vaginal swabs. Lactobacillus sp. and their probiotic culture free supernatant (PCFS) inhibited the growth of the above-mentioned urogenital pathogens. L. crispatus produced both lactic acid and hydrogen peroxide, exhibiting the best antimicrobial potential against the studied pathogens. Lyophilized L. crispatus had a shelf life of 12 months and the lyophilized PCFS also retained its antibacterial property with a minimum inhibition concentration of 1 µg/µL. Carboxy-methyl cellulose-alginate, a green alternative to super-absorbent polymers, was encapsulated with L. crispatus cells. The probiotic in its encapsulated state retained its viability for 21 days, and the bead showed 30% solvent absorptive capacity. PCFS-laced non-woven fabric displayed antibacterial property with no change in its physicochemical properties. These probiotic and postbiotic formulations have excellent prophylactic potential for urogenital infections. Such formulations can be exploited as additives in sanitary suppositories to enhance vaginal health.

History of Rectal Product Use and Country of Residence Influence Preference for Rectal Microbicide Dosage Forms Among Young Sexual and Gender Minorities: A Multi-country Trial Comparing Placebo Douche, Suppository, and Insert Products.

The DESIRE Study (MTN-035) explored product preference among three placebo rectal microbicide (RM) formulations, a rectal douche (RD), a suppository, and an insert, among 210 sexually active transgender people and men who have sex with men in five counties: the United States, Peru, Thailand, South Africa, and Malawi. Participants used each product prior to receptive anal sex (RAS) for 1 month, following a randomly assigned sequence, then selected their preferred product via computer assisted self-interview. In-depth interviews examined reasons for preference. We compared product preference and prior product use by country to explore whether geographic location and experience with the similar products impacted preference. A majority in the United States (56%) and Peru (58%) and nearly half in South Africa (48%) preferred the douche. Most in Malawi (59%) preferred the suppository, while half in Thailand (50%) and nearly half in South Africa (47%) preferred the insert. Participants who preferred the douche described it as quick and easy, already routinized, and serving a dual purpose of cleansing and protecting. Those who preferred the insert found it small, portable, discreet, with quick dissolution. Those who preferred the suppository found the size and shape acceptable and liked the added lubrication it provided. Experience with product use varied by country. Participants with RD experience were significantly more likely to prefer the douche (p = 0.03). Diversifying availability of multiple RM dosage forms can increase uptake and improve HIV prevention efforts globally.

RESUMEN: El estudio DESIRE (MTN-035) exploró la preferencia de producto entre tres formulaciones de microbicida rectal (MR) de placebo, una ducha rectal, un supositorio y un inserto, entre 210 personas transgénero y hombres que tienen sexo con hombres en cinco países: los Estados Unidos, Perú., Tailandia, Sudáfrica y Malawi. Los participantes utilizaron cada producto antes del sexo anal receptive (SAR) durante un mes, siguiendo una secuencia asignada al azar, luego seleccionaron su producto preferido mediante una autoentrevista asistida por computadora. Las entrevistas en profundidad examinaron los motivos de preferencia. Comparamos la preferencia de producto y el uso previo del producto por país para explorar si la ubicación geográfica y la experiencia con la forma farmacéutica impactaron la preferencia. Una mayoría en los Estados Unidos (56%) y Perú (58%) y casi la mitad en Sudáfrica (48%) prefirieron la ducha rectal. La mayoría en Malawi (59%) prefirió el supositorio, mientras que la mitad en Tailandia (50%) y casi la mitad en Sudáfrica (47%) prefirió el inserto. Los participantes que prefirieron la ducha rectal la describieron como rápida y fácil, ya parte de su rutina y que tenía el doble propósito de limpiar y proteger. Los que prefirieron el inserto lo consideraron pequeño, portátil, discreto y de rápida disolución. Los que prefirieron el supositorio encontraron que tenía un tamaño y forma aceptables y proveía lubricación adicional. La experiencia con el uso del producto varió según el país. Los participantes con experiencia con duchas rectales tenían significativamente más probabilidades de preferir la ducha rectal (p = 0,03). Diversificar la disponibilidad de múltiples formas farmacéuticas de MR puede aumentar la aceptación y mejorar los esfuerzos de prevención del VIH a nivel mundial.

Effectiveness and tolerability of rectal ointment and suppositories containing sucralfate for hemorrhoidal symptoms: a prospective, observational study.

BACKGROUND AND AIMS: A high number of topical products are available for the treatment of hemorrhoidal symptoms. Sucralfate-based topical products constitute a new treatment alternative that act as a mechanical barrier to facilitate healing. The aim of this prospective, observational study was to determine patient- and physician-assessed effectiveness and tolerability of rectal ointment and suppositories containing sucralfate for the treatment of hemorrhoidal symptoms in routine clinical practice. METHODS: Adult patients with diagnosed, mild-to-moderate, symptomatic non-bleeding hemorrhoids treated with rectal ointment or suppositories containing sucralfate were enrolled. Patients were administered treatment twice per day for at least 1 week until symptom resolution and/or for a maximum of 4 weeks. The primary endpoint was patient-assessed effectiveness on a modified Symptom Severity Score (mSSS, range 0 to 14). Physician-assessed effectiveness (9 symptoms, 0 to 5 Likert scale), hemorrhoid grade, and patient satisfaction were also determined. RESULTS: Five investigators enrolled 60 patients; mean age was 48.4 ± 16.6 years and 72.4% were female. Pain or pressure sensitivity was reported as the most severe symptom by patients, and pressure sensitivity, discharge, soiling, and prolapse by physicians. Mean patient-assessed mSSS at baseline was 6.6 ± 1.9 and was significantly improved overall and in the ointment and suppository groups individually by -4.6 ± 2.0, -4.4 ± 1.8, and -4.8 ± 2.2, respectively (p < 0.0001). Investigator-assessed mean baseline symptom score was 18.1 ± 3.9 and improved by -7.1 ± 4.5, -6.9 ± 5.4, and -7.3 ± 3.5, respectively (p < 0.0001). Investigator-assessed symptoms of pressure sensitivity, swelling, and discharge were improved to the greatest extent. Hemorrhoid grade was improved in 38% of patients at the end of treatment. Compliance with treatment was 97.4% and patient satisfaction with application and onset of action was high (81.3% and 76.2%, respectively). Both the ointment and suppository were well tolerated. CONCLUSIONS: The effectiveness of topical ointment or suppository containing sucralfate on patient- and investigator-assessed hemorrhoidal symptoms in real-life clinical practice was demonstrated. Patient satisfaction was high and treatments were well tolerated. Larger controlled trials are warranted to confirm the results.

Sertaconazole 300 mg versus clotrimazole 500 mg vaginal suppository for treating pregnant women with acute vaginal candidiasis: a double-blinded, randomized trial.

BACKGROUND: Vaginal candidiasis (VC) commonly affects pregnant women. Traditionally, clotrimazole vaginal tablets (CLO) have been the cornerstone of management. However, sertaconazole ovules (SER) offer a novel topical antimycotic option. This double-blinded, randomized trial evaluated the efficacy of single-dose SER and CLO in treating acute VC during pregnancy. METHODS: From June 2020 to May 2021, this trial recruited pregnant women aged ≥ 18 years with VC symptoms (abnormal vaginal discharge and/or vulvar/vaginal itching) confirmed by microscopy. Participants with ≥ 4 VC episodes in the prior year, immunocompromised status, or imidazole contraindications and those who were absent at the 2-week follow-up were excluded. Participants were randomized to receive either 300 mg SER or 500 mg CLO. Evaluations 2 weeks after the initial medication administration included clinical cure (self-reported resolution of all symptoms), microscopic cure (pseudohyphal absence), patient satisfaction, side effects, and time to clinical cure. Participants with persistent VC received weekly SER doses until delivery. Assessments of recurrence and pregnancy outcomes were done. RESULTS: The analysis included 96 participants (48 per group, mean age 27.4 ± 7.4 years, gestational age at diagnosis 22.9 ± 6.4 weeks). Without statistical significance, SER achieved a higher clinical cure rate (62.5% vs 50%, p = 0.217; a mean difference of 12.5%, 95%CI: -17.5% to 42.5%; and a rate ratio of 1.25, 95%CI: 0.71 to 2.23) and a lower microscopic cure (47.9% vs. 62.5%, p = 0.151; a mean difference of -14.6%, 95%CI: -44.3% to 15.1%; and a rate ratio of 0.77, 95%CI: 0.43 to 1.37). The two groups had comparable times to clinical cure (SER: 3.1 ± 1.8 days, CLO: 3.4 ± 2.7 days; p = 0.848) and substantial satisfaction rates (SER: 66.7%, CLO: 60.4%; p = 0.753). No side effects were reported. Of 60 participants who gave birth at Siriraj Hospital, there were no significant differences in pregnancy outcomes. Repeated SER dosing eradicated symptoms and enhanced the microscopic cure rate. Recurrence was observed in four SER and two CLO participants within 1-2 months. CONCLUSION: In the treatment of acute VC during pregnancy, 300 mg SER and 500 mg CLO exhibited comparable efficacy in terms of clinical and microscopic cure rates, satisfaction, side effects, time to clinical cure, recurrence rates, and pregnancy outcomes. TRIAL REGISTRATION: TCTR20190308004 (registration date March 8, 2019).

Effect of Clotrimazole Suppositories on Distribution of Pathogens in Vaginal Secretions and Oxidative Stress in Patients with Vaginitis.

Objective: To evaluate the impact of clotrimazole suppositories on the distribution of vaginal pathogens and oxidative stress in patients with vaginitis. Methods: A total of 120 patients with vaginitis were recruited from our hospital between January 2021 and December 2022 and were divided into an observation group and a control group using a random envelope method. The control group received treatment with miconazole tablets alone, while the observation group received combined treatment with miconazole tablets and clotrimazole suppositories. Vaginal secretions were collected from the subjects for pathogenic microbial testing. The clinical efficacy of the patients was evaluated, and indicators related to vaginal microecology and microbial imbalance were examined. Serum levels of IL-8, CRP, TNF-α, IL-6, PCT, P, LH, FSH, SOD, MDA, NO, and ET-1 were measured in the subjects. Results: Among patients with vaginitis, bacteria, fungi, and gram-negative cocci accounted for a relatively high proportion, with bacterial infections accounting for more than 30% and fungal and gram-negative cocci infections both exceeding 10%. Pathogenic infections such as Chlamydia and Trichomonas were less than 10%. The observation group showed significantly higher clinical efficacy compared to the control group, with a statistically significant difference (P < .05). Following treatment, the observation group exhibited significantly lower scores for itching, vaginal discharge, and burning sensation compared to the control group, with a statistically significant difference (P < .05). After treatment, the observation group had significantly lower bacterial density and Nugent score, higher cleanliness, positive lactobacilli rate, and pH value compared to the control group, and the difference was statistically significant (P < .05). After treatment, the observation group demonstrated significantly lower blood levels of IL-8, CRP, TNF-α, IL-6, and PCT compared to the control group, with a statistical significance of P < .05. Similarly, the levels of P, LH, and FSH hormones in the observation group were significantly lower than those in the control group, also with a statistical significance of P < .05. In contrast, the levels of SOD and NO in the observation group were significantly higher, while the levels of MDA and ET-1 were significantly lower compared to the control group, with a statistical significance of P < .05. Conclusion: Clotrimazole suppositories have been shown to significantly enhance therapeutic outcomes for patients with vaginitis by alleviating inflammation, rebalancing vaginal microecology, regulating hormone secretion, and mitigating oxidative stress.

The effects of various therapies on vulvovaginal atrophy and quality of life in gynecological cancer patients: a systematic review.

PURPOSE: Tumors affecting the female genital tract and their treatments have the potential to induce adverse modifications in vaginal health and impact personal aspects of patient's lives. Vulvovaginal atrophy is one of the morphological changes observed in individuals with a history of gynecological cancer, influenced both by the biological environment of tumors and the main therapeutic modalities employed. Therefore, the purpose of this study was to identify approaches to treat vulvovaginal atrophy while assessing the impact on the emotional and sexual health of women diagnosed with gynecological cancers. METHODS: To achieve this goal, a systematic review was conducted following the methodological guidelines outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The databases used for literature research were PubMed and Web of Science. RESULTS: Initially, 886 articles were obtained. After eliminating duplicates and applying inclusion/exclusion criteria, seven articles were selected for analysis. The period of highest publication activity spanned from 2017 to 2020, with the majority conducted in Italy. Five treatment modalities were identified and categorized as vaginal suppository, oral medication, surgical procedure, CO2 laser therapy, and vaginal dilator. Twenty-four outcomes related to vaginal health and 30 outcomes related to overall, sexual, and emotional quality of life were analyzed. CONCLUSION: In general, all interventions demonstrated the ability to improve vaginal health or, at the very least, the sexual health of patients. Thus, despite limitations, all treatments have the potential to address vulvovaginal atrophy in patients with a history of gynecological cancer.

Lipid-Gelucire based rectal delivery of ramipril prodrug exhibits significant lowering of intra-ocular pressure in normotensive rabbit: sustained structural relaxation release kinetics and IVIVC.

Carboxylesterase enzymes convert a prodrug ramipril into the biologically active metabolite ramiprilat. It is prescribed for controlling ocular hypertension after oral administration. High concentrations of carboxylesterase enzymes in rectal and colon tissue can transform ramipril significantly to ramiprilat. Sustained rectal delivery of ramipril has been developed for intra-ocular pressure lowering effect using a normotensive rabbit model. Rectal suppositories have been formulated using a matrix base of HPMC K100-PEG 400-PEG 6000, incorporating varying amounts of Gelucire by the fusion moulding method. The presence of Gelucire in the suppository exhibited sustained structural relaxation-based release kinetics of RM compared to its absence. Intravenous and oral administration of ramipril has decreased IOP in the treated rabbit up to 90 and 360 min, respectively. Treated rabbits with suppositories have revealed decreased IOP for an extended period compared to the above. Formulation containing GEL 3% reduced intra-ocular pressure to 540 min, with the highest area under the decreased IOP curve. Compared to oral, the pharmacodynamic bioavailability of ramipril has been improved significantly using a sustained-release rectal suppository. A rectal suppository for sustained delivery of ramipril could be used to lower IOP significantly.

Rectal artesunate suppositories for the pre-referral treatment of suspected severe malaria.

In this Policy Forum article, James A. Watson and colleagues discuss recent guidelines relating to pre-referral treatment of suspected severe malaria with rectal artesunate suppositories in remote areas.

Menopausal hormone therapy and risk of biliary tract cancers.

BACKGROUND AND AIMS: Gallbladder cancer (GBC) has a female predominance, whereas the other biliary tract cancers (BTCs) have a male predominance, suggesting that sex hormones may be involved in carcinogenesis. We sought to evaluate the association between menopausal hormone therapy (MHT) and the risk of BTC in women. APPROACH AND RESULTS: This nested case-control study was conducted in the UK Clinical Practice Research Datalink. Cases diagnosed between 1990 and 2017 with incident primary cancers of the gallbladder (GBC), cholangiocarcinoma (CCA), ampulla of Vater (AVC), and mixed type were matched to 5 controls on birth year, diagnosis year, and years in the general practice using incidence density sampling. Conditional logistic regression was used to calculate ORs and 95% CIs for associations between MHT use and BTC type. The sample consisted of 1,682 BTC cases (483 GBC, 870 CCA, 105 AVC, and 224 mixed) and 8,419 matched controls with a mean age of 73 (SD, 11) years. Combined formulations (estrogen-progesterone) were associated with an increased GBC risk (OR, 1.97; 95% CI, 1.08, 3.59). Orally administered MHT was associated with an increased GBC risk (OR, 2.28; 95% CI, 1.24, 4.17). Estrogen-only formulations (OR, 0.59; 95% CI, 0.34, 0.93) and cream or suppository administrations (OR, 0.57; 95% CI, 0.34, 0.95) were associated with decreased CCA risk. The number of prescriptions, dose, duration of use, and time since last use were not associated with GBC or CCA risk. MHT use was not associated with risk of AVC or mixed cancer. CONCLUSIONS: Combination MHT formulations and oral administrations were associated with increased GBC risk, whereas estrogen-only formulations were associated with a lower CCA risk. MHT formulation and administration should be carefully considered when prescribing.

Improving Bowel Management in Children With Spina Bifida.

OBJECTIVES: In individuals with spina bifida (SB), bowel incontinence is associated with lower quality of life and lower likelihood of employment. In an effort to maximize bowel continence in children and adolescents, we created a bowel management assessment and follow-up protocol in a multidisciplinary clinic. Here we report the results of this protocol using quality-improvement methodology. METHODS: Continence was defined as no unplanned bowel movements. Our protocol involved: (1) a standardized 4-item questionnaire about bowel continence and consistency; (2) if the patient was not achieving continence, an intervention starting with oral medication (stimulant and/or osmotic laxatives), and/or suppositories (glycerin or bisacodyl) followed by an escalation to trans-anal irrigation, or continence surgery; and (3) follow-up phone calls at regular intervals to monitor progress and make changes as needed. Results are summarized with descriptive statistics. RESULTS: We screened 178 eligible patients in the SB clinic. Eighty-eight agreed to participate in the bowel management program. Of those who did not participate, the majority (68/90, 76%) were already achieving continence with their bowel regimen. Of children in the program, most (68/88, 77%) had a diagnosis of meningomyelocoele. At 1 year, the proportion of patients who were bowel accident free improved to 46% (vs 22% initially, P = 0.0007). CONCLUSIONS: A standardized bowel management protocol, primarily the use of suppositories and trans-anal irrigation to achieve social continence, as well as frequent telephone follow-up, can reduce bowel incontinence in children and adolescents with SB.

Can vaginal lactobacillus suppositories help reduce urinary tract infections?

INTRODUCTION AND HYPOTHESIS: Recurrent urinary tract infections (rUTIs) are a burden to patients and the health care economy. Vaginal probiotics and supplements have gained significant attention in mainstream media and lay press as a non-antibiotic alternative. We performed a systematic review to determine whether vaginal probiotics are an effective means of prophylaxis for rUTI. METHODS: A PubMed/MEDLINE article search was performed from inception to August 2022 for prospective, in vivo use of vaginal suppositories for the prevention of rUTIs. Search terms included: vaginal probiotic suppository (34 results), vaginal probiotic randomized (184 results), vaginal probiotic prevention (441 results), vaginal probiotic UTI (21 results), and vaginal probiotic urinary tract infection (91 results). A total of 771 article titles and abstracts were screened. RESULTS: A total of 8 articles fit the inclusion criteria and were reviewed and summarized. Four were randomized controlled trials, with 3 of the studies having a placebo arm. Three were prospective cohort studies, and 1 was a single arm, open label trial. Five of the 7 articles that specifically evaluated for rUTI reduction with vaginal suppositories did find a decreased incidence with probiotic use; however, only 2 had statistically significant results. Both of these were studies of Lactobacillus crispatus and were not randomized. Three studies demonstrated the efficacy and safety of Lactobacillus as a vaginal suppository. CONCLUSION: Current data support the use of vaginal suppositories containing Lactobacillus as a safe, non-antibiotic measure, but actual reduction of rUTI in susceptible women remains inconclusive. The appropriate dosing and duration of therapy remain unknown.

[The efficiency of various cytokine therapy regimens in the complex treatment of men with chronic abacterial prostatitis].

INTRODUCTION: Chronic prostatitis (CP) is one of the most important and discussed urological diseases. Treatment of bacterial CP with an established pathogen usually is not associated with any difficulties. Chronic abacterial prostatitis (CAP) remains the most problematic issue. Immune defense mechanisms are important in the development of CP, including a decrease in the functional activity of monocytes/ macrophages, neutrophils, as well as imbalance of pro- and anti-inflammatory cytokines. AIM: To evaluate the efficiency of various schemes of using the immunomodulatory drug Superlymph as part of the combination therapy of men with CAP. MATERIALS AND METHODS: A total of 90 patients with category IIIa CAP (NIH, 1995) were included in the study. In the control group, patients received basic therapy of CAP, namely behavioral therapy, 1-adrenoblocker and fluoroquinolone for 28 days. In the main group I basic therapy in combination with Superlymph 25 ME in one suppository q.d. for 20 days was administered. In the main group II basic therapy in combination with Superlymph 10 ME in one suppository b.i.d. for 20 days was given. Evaluation of treatment efficiency was carried out after 14 +/- 2 days (visit 2) and 28+/- 2 days (visit 3) from the start of treatment. RESULTS: The study groups were homogeneous, and baseline characteristics did not differ significantly (p>0.05). However, significant differences were found between the results in the main groups and the control group at visit 2 for all the indicators (p<0.05). The number of daytime urinations was lower in the main group I and II compared to CG by 16.7% and 28.4%, the number of night urination by 28% and 40%, the average IPSS score by 29.1% and 38.3%, the average QoL score by 32.4% and 45.9%, the average NIH-CPSI score by 26.8% and 37.4%, the number of leukocytes in expressed prostatic secretion by 41.2% and 52.1%, prostate volume by 16.8% and 21.8%, bladder volume by 15.8% and 21.7%, and Qmax by 14.3% and 21.2%, respectively. Similar significant differences between the main groups and control group were also seen at visit 3, while the indicators in main groups I and II reached normal values after 28 days of therapy. In this study, for the first time, a comparative analysis of two different treatment regimens with Superlymph was carried out. In the main group I, patients received suppositories at a dose of 25ME q.d., while in the main group II, the drug was administered 10 ME b.i.d. The results indicate a comparable efficiency of both schemes after 4 weeks. However, in the main group II, after 2 weeks, there was a significantly more pronounced positive dynamics of all indicators in comparison with the main group I (p<0.05). Consequently, the use of Superlymph at a dose of 10ME b.i.d. a day allows to reduce the severity of the inflammatory process in a shorter time. CONCLUSION: The use of Superlymph in patients with CAP allows to reduce the severity of clinical manifestations in a shorter time, and has a positive effect on the dynamics of the inflammatory process, which leads to an improvement in the quality of life. According to our results, the most effective scheme in patients with CAP is basic therapy in combination with Superlymph 10 ME for 1 suppository 2 times a day for 10 days. In our opinion, Superlymph can be effectively used as part of the combination therapy of men with CAP.

[Spermoprotective properties of Prostatex in patients with chronic abacterial prostatitis].

AIM: To study the effect of Prostatex therapy on spermatogenesis in patients with infertility that developed due to chronic abacterial prostatitis. MATERIALS AND METHODS: A total of 60 men with infertility in marriage and chronic abacterial prostatitis were included in the study. All patients received therapy with Prostatex rectal suppositories 10 mg 1 time per day. The duration of treatment was 30 days. After taking the drug, patients were observed for 50 days. The study was carried out for 80 days and included 3 visits at 1, 30 and 80 days. The study showed that the use of Prostatex rectal suppositories 10 mg had a positive effect on the main indicators of spermatogenesis, as well as on the subjective and objective symptoms of chronic abacterial prostatitis. Based on these results, we recommend Prostatex rectal suppositories to patients with chronic abacterial prostatitis, accompanied by impaired spermatogenesis, according to the scheme: 1 suppository 10 mg 1 time per day for 30 days.

[Chronic cystitis: how to prolong the relapse-free period?]

INTRODUCTION: Chronic cystitis predominates in the structure of urinary tract infections (UTIs). International guidelines are mainly focused on the treatment of acute uncomplicated cystitis; the approaches for managing patients with chronic cystitis has not been sufficiently developed. MATERIAL AND METHODS: A total of 91 patients were included in prospective multicenter randomized comparative controlled study. They were divided into three groups. In the group 1, 32 women received only standard antibiotic therapy for 5 days. In the group 2, 28 patients (received standard therapy plus rectal suppositories Superlymph 25 IU 1 time per day for 10 days). In the main group, 31 women received standard therapy in combination with the use of rectal suppositories Superlymph at a dose of 10 IU 1 time per day for 20 days. Standard antibiotic therapy included fosfomycin trometamol 3.0 g once and furazidin 100 mg three times for 5 days. To assess the long-term results, patients were invited for a follow-up 6 months after the end of therapy. AIM: To determine the long-term results of combined etiologic and pathogenetic therapy, including Superlymph rectal suppositories at a dose of 10 U and 25 U, in patients with chronic cystitis. RESULTS: Six months later, 82/91 (90.1%) women were examined to assess the long-term results. At 6 months, in group 1 a relapse of the cystitis developed in 17 women (60.7%) after an average of 67.3+/-9.4 days. In group 2, recurrence was observed in 12 patients (44.4%), and the relapse-free period was longer, averaging of 84.3+/-9.2 days. The best results were demonstrated in the main group, in which the relapse-free period lasted an average of 123.5+/-8.7 days, and a relapse developed in only 8 cases (29.6%). In 19 patients (70.4%) there were no symptoms after six months. Differences between groups were highly significant (p<0.001). In all groups, none of the patients had more than one recurrence of the cystitis during the follow-up. CONCLUSION: Combined antibiotic therapy results in the absence of recurrence within six months in 39.3% of patients with chronic cystitis. Complex etiologic and pathogenetic therapy, including Superlymph rectal suppositories, allows to significantly reduce the number of recurrences and prolong the relapse-free period. Among the patients who received a course of local cytokine therapy at a dose of 25 units for 10 days, 55.6% did not have a recurrence of chronic cystitis within 6 months. In the group of patients who, along with etiologic therapy, received Superlymph rectal suppositories at a dose of 10 IU for 20 days, a relapse was absent in 70.4% of patients.

[Onto-phylogenetic prerequisites for development of chronic cystitis in women].

INTRODUCTION: Urinary tract infections (UTIs) are among the most common bacterial infections. At the request "cystitis", there are 12,067 publications in the RSCI system (e.library) as of 10/08/2023 and 16,332 articles were screened in the Pubmed. This is evidence that the problem of cystitis is far from being resolved. MATERIAL AND METHODS: A total of 425 patients with bacterial vaginosis and 77 women with chronic recurrent cystitis were included in the study. In all patients, the vaginal biocenosis was assessed through molecular genetic testing. The examination included filling out the Russian version of the Acute Cystitis Symptom Score (ACSS), urinalysis, and urine culture. In addition, local microcirculation was measured using laser Doppler flowmetry (LDF). After examination, patients were prescribed basic therapy and randomly assigned to one of three groups. In a control group (n=17), only basic therapy, consisting of fosfomycin 3.0 once at night + furagin 100 mg after meals 3 times a day for 5 days was prescribed. In the main group 1, 29 women received basic therapy plus Superlymph suppositories 10 units 2 times a day vaginally for 10 days. In the main group 2, 31 patients received basic therapy plus suppositories Superlymph 10 units (rectally in the morning) and Acylact Duo (vaginally in the evening) for 10 days. RESULTS: Among 425 patients with bacterial vaginosis, 78 (18.3%) complained of various urinary disorders, but only 21 women (4.9% of those with vaginal dysbiosis and 26.9% with dysuria) had a diagnosis of cystitis. In all cases, it was an exacerbation of a chronic disease. Among 77 patients with chronic cystitis, normal vaginal flora was initially present in 32 patients (41.6%), and bacterial vaginosis was found in 45 (58.4%) cases. After therapy, positive results were noted in patients of all groups. Complete eradication of the pathogen occurred in 15 women (88.2%) who received only basic therapy; in the main groups 1 and 2, uropathogens were not detected in 27 (93.1%) and 28 (90.3%) cases, respectively. In the control group, the proportion of patients with normal vaginal flora remained virtually unchanged (41.2% [n=7] vs. 47.1% [n=8]). In the main group 1, the proportion of patients with normal vaginal flora almost doubled: from 41.4% (n=12) to 79.3% (n=23). In main group 2, restoration of vaginal flora was noted in 87.1% of cases. CONCLUSION: According to our data, only 4.9% of patients with bacterial vaginosis were diagnosed with chronic cystitis, however, 58.4% of patients with chronic cystitis had vaginal dysbiosis. The use of a complex of antimicrobial peptides and cytokines has significantly increased the bidirectional effect of therapy. Suppositories Superlymph in a combination with vaginal use of Acylact Duo allow to obtain the best results.

Efficacy, safety, and economic impact of diazepam suppositories with as-needed acetaminophen for prevention of seizure recurrence during the same fever episode in children with suspected simple febrile seizures.

OBJECTIVE: This study was undertaken to evaluate the efficacy, safety, and economic impact of diazepam suppositories with as-needed acetaminophen in comparison with as-needed acetaminophen alone for prevention of seizure recurrence during the same fever episode in suspected pediatric simple febrile seizures (SFS). METHODS: This single-center, prospective, observational study was conducted from July 29, 2019 to February 15, 2021 at a children's hospital. Children aged 6 months to 60 months presenting to the emergency department with suspected SFS were included. Participants receiving both diazepam suppositories and as-needed acetaminophen were compared with those receiving as-needed acetaminophen alone. The primary outcome was seizure recurrence during the same fever episode. The secondary outcomes included the incidence of central nervous system (CNS) pathologies, adverse events, and medical costs. RESULTS: Of the 316 participants, 228 (72.2%) had their first febrile seizure. Diazepam (.3-.5 mg/kg for up to two doses) was administered to 88 of 316 patients (27.8%). The outcomes were available for 306 patients. The recurrence rate was 3.5% (3/85) in the patients receiving diazepam with as-needed acetaminophen and 12.2% (27/221) in the patients receiving as-needed acetaminophen alone (relative risk = .29, 95% confidence interval [CI] = .09-.93, p = .03). The adjusted odds ratio of diazepam administration against recurrence was .23 (95% CI = .07-.78, p = .02). None of the patients had a CNS pathology. No severe adverse events occurred, although mild ataxia was observed significantly more often in the patients receiving diazepam and as-needed acetaminophen (29.4% vs. 18.7%, p = .04). The median medical cost was US $199 (interquartile range [IQR] = 86-244) for the group receiving both medications and US $202 (IQR = 114-242) for the group receiving as-needed acetaminophen alone. SIGNIFICANCE: Compared with as-needed acetaminophen alone, diazepam with as-needed acetaminophen may reduce seizure recurrence more during the same fever episode without severe adverse events or additional costs in children with suspected SFS.

Pre-referral intranasal artesunate powder for cerebral malaria: a proof-of-concept study.

BACKGROUND: Malaria still kills young children in rural endemic areas because early treatment is not available. Thus, the World Health Organization recommends the administration of artesunate suppositories as pre-referral treatment before transportation to the hospital in case of severe symptoms with an unavailable parenteral and oral treatment. However, negative cultural perception of the rectal route, and limited access to artesunate suppositories, could limit the use of artesunate suppositories. There is, therefore, a need for an alternative route for malaria pre-referral treatment. The aim of this study was to assess the potential of intranasal route for malaria pre-referral treatment. METHODS: The permeability of artesunate through human nasal mucosa was tested in vitro. The Transepithelial Electrical Resistance (TEER) of the nasal mucosa was followed during the permeation tests. Beside, regional deposition of artesunate powder was assessed with an unidose drug delivery device in each nostril of a nasal cast. Artesunate quantification was performed using Liquid Chromatography coupled to tandem Mass Spectrometry. RESULTS: The experimental model of human nasal mucosa was successfully implemented. Using this model, artesunate powder showed a much better passage rate through human nasal mucosa than solution (26.8 ± 6.6% versus 2.1 ± 0.3%). More than half (62.3%) of the artesunate dose sprayed in the nostrils of the nasal cast was recovered in the olfactory areas (44.7 ± 8.6%) and turbinates (17.6 ± 3.3%) allowing nose-to-brain and systemic drug diffusion, respectively. CONCLUSION: Artesunate powder showed a good permeation efficiency on human nasal mucosa. Moreover it can be efficiently sprayed in the nostrils using unidose device to reach the olfactory area leading to a fast nose-to-brain delivery as well as a systemic effect. Taken together, those results are part of the proof-of-concept for the use of intranasal artesunate as a malaria pre-referral treatment.

Tacrolimus (FK506) for induction of remission in corticosteroid-refractory ulcerative colitis.

BACKGROUND: There are a limited number of treatment options for people with corticosteroid-refractory ulcerative colitis. Animal models of inflammatory bowel disease and uncontrolled studies in humans suggest that tacrolimus may be an effective treatment for ulcerative colitis. OBJECTIVES: To evaluate the efficacy and safety of tacrolimus for induction of remission in people with corticosteroid-refractory ulcerative colitis. SEARCH METHODS: We searched the Cochrane Gut group specialised register, CENTRAL, MEDLINE (PubMed), Embase, Clinicaltrials.gov and WHO ICTRP from inception to October 2021 to identify relevant randomised controlled trials (RCT). SELECTION CRITERIA: Two review authors independently selected potentially relevant studies to determine eligibility based on the prespecified criteria. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and analysed them using Review Manager Web. The primary outcomes were induction of remission and clinical improvement, as defined by the studies and expressed as a percentage of the participants randomised (intention-to-treat analysis). MAIN RESULTS: This review included five RCTs with 347 participants who had active ulcerative colitis or ulcerative proctitis. The duration of intervention varied between two weeks and eight weeks. Tacrolimus versus placebo Tacrolimus (oral and rectal) may be superior in achieving clinical remission compared to placebo (oral and rectal) (14/87 participants with tacrolimus versus 1/61 participants with placebo; risk ratio (RR) 3.76, 95% confidence interval (CI) 1.03 to 13.73; 3 studies). These results are of low certainty due to imprecision and risk of bias. Tacrolimus (oral and rectal) may be superior for clinical improvement compared to placebo (oral and rectal) (45/87 participants with tacrolimus versus 7/61 participants with placebo; RR 4.47, 95% CI 2.15 to 9.29; 3 studies). These results are of low certainty due to imprecision and risk of bias. The evidence is very uncertain about the effects of tacrolimus (oral and rectal) on serious adverse events compared to placebo (oral and rectal) (2/87 participants with tacrolimus versus 0/61 participants with placebo; RR 2.44, 95% CI 0.12 to 48.77; 3 studies). These results are of very low certainty due to high imprecision and risk of bias. Tacrolimus versus ciclosporin One study compared oral tacrolimus to intravenous ciclosporin, with an intervention lasting two weeks and 113 randomised participants. The evidence is very uncertain about the effect of tacrolimus on achievement of clinical remission compared to ciclosporin (15/33 participants with tacrolimus versus 24/80 participants with ciclosporin; RR 1.52, 95% CI 0.92 to 2.50). The results are of very low certainty due to risk of bias and high imprecision. The evidence is very uncertain about the effect of tacrolimus on clinical improvement compared to intravenous ciclosporin (23/33 participants with tacrolimus versus 62/80 participants with ciclosporin; RR 0.90, 95% CI 0.70 to 1.16). The results are of very low certainty due to risk of bias and imprecision. Tacrolimus versus beclometasone One study compared tacrolimus suppositories with beclometasone suppositories in an intervention lasting four weeks with 88 randomised participants. There may be little to no difference in achievement of clinical remission (16/44 participants with tacrolimus versus 15/44 participants with beclometasone; RR 1.07, 95% CI 0.60 to 1.88). The results are of low certainty due to high imprecision. There may be little to no difference in clinical improvement when comparing tacrolimus suppositories to beclometasone suppositories (22/44 participants with tacrolimus versus 22/44 with beclometasone; RR 1.00, 95% CI 0.66 to 1.52). The results are of low certainty due to high imprecision. There may be little to no difference in serious adverse events when comparing tacrolimus suppositories to beclometasone suppositories (1/44 participants with tacrolimus versus 0/44 with beclometasone; RR 3.00, 95% CI 0.13 to 71.70). These results are of low certainty due to high imprecision. There may be little to no difference in total adverse events when comparing tacrolimus suppositories to beclometasone suppositories (21/44 participants with tacrolimus versus 14/44 participants with beclometasone; RR 1.50, 95% CI 0.88 to 2.55). These results are of low certainty due to high imprecision. No secondary outcomes were reported for people requiring rescue medication or to undergo surgery. AUTHORS' CONCLUSIONS: There is low-certainty evidence that tacrolimus may be superior to placebo for achievement of clinical remission and clinical improvement in corticosteroid-refractory colitis or corticosteroid-refractory proctitis. The evidence is very uncertain about the effect of tacrolimus compared to ciclosporin for achievement of clinical remission or clinical improvement. There may be no difference between tacrolimus and beclometasone for inducing clinical remission or clinical improvement. The cohorts studied to date were small, with missing data sets, offered short follow-up and the clinical endpoints used were not in line with those suggested by regulatory bodies. Therefore, no clinical practice conclusions can be made. This review highlights the need for further research that targets the relevant clinical questions, uses appropriate trial methodology and reports key findings in a systematic manner that facilitates future integration of findings with current evidence to better inform clinicians and patients. Future studies need to be adequately powered and of pertinent duration so as to capture the efficacy and effectiveness of tacrolimus in the medium to long term. Well-structured efficacy studies need to be followed up by long-term phase 4 extensions to provide key outputs and inform in a real-world setting.

The efficacy of a suppository based on Phenolmicin P3 and Bosexil (Mictalase®) in control of irritative symptoms in patients undergoing thulium laser enucleation of prostate: a single-center, randomized, controlled, open label, phase III study.

BACKGROUND: Several studies described post-operative irritative symptoms after laser enucleation of prostate, sometimes associated with urge incontinence, probably linked to laser-induced prostatic capsule irritation, and potential for lower urinary tract infections We aimed to evaluate the efficacy of a suppository based on Phenolmicin P3 and Bosexil (Mictalase®) in control of irritative symptoms in patients undergoing thulium laser enucleation of prostate (ThuLEP). METHODS: In this single-center, prospective, randomized, open label, phase-III study, patients with indication to ThuLEP were enrolled (Dec2019-Feb2021-Institutional ethics committee STS CE Lazio approval no.1/N-726-ClinicalTrials.gov NCT05130918). The report conformed to CONSORT 2010 guidelines. Eligible patients were 1:1 randomized. Randomization defined Group A: patients who were administered Mictalase® suppositories twice a day for 5 days, then once a day for other 10 days; Group B: patients who did not receive Mictalase® ("controls"). Study endpoints were evaluated at 15 and 30 days postoperation. Primary endpoint included evaluation of effects of the suppository on irritative symptoms by administering IPSS + QoL questionnaire. Secondary endpoint included evaluation of effects on urinary tract infections by performance of urinalysis with urine culture. RESULTS: 111 patients were randomized: 56 in Group A received Mictalase®. Baseline and perioperative data were comparable. At 15-days, no significant differences were found in terms of IPSS + QoL scores and urinalysis parameters. A significant difference in the rate of positive urine cultures favored Group A (p = 0.04). At 30-days follow-up, significant differences were found in median IPSS score (6 [IQR 3-11] versus 10 [5-13], Group A vs B, respectively, p = 0.02). Urinalysis parameters and rate of positive urine cultures were not significantly different. CONCLUSIONS: The present randomized trial investigated the efficacy of Mictalase® in control of irritative symptoms and prevention of lower urinary tract infections in patients undergoing ThuLEP. IPSS improvement 30-days postoperation was more pronounced in patients who received Mictalase®. Lower rate of positive urine culture favored Mictalase® group 15-days postoperatively. TRIAL REGISTRATION: The clinical trial has been registered on ClinicalTrials.gov on November 23rd, 2021-Registration number NCT05130918.

Development and Comprehensive Characteristics of Thermosensitive Liquid Suppositories of Metoprolol Based on Poly(lactide-co-glycolide) Nanoparticles.

Thermosensitive liquid suppositories (LSs) carrying the model antihypertensive drug metoprolol tartrate (MT) were developed and evaluated. The fundamental purpose of this work was to produce, for the first time, liquid MT suppositories based on biodegradable nanoparticles and optimize their rheological and mechanical properties for prospective rectal administration. The nanoparticle system was based on a biodegradable copolymer synthesized by ring opening polymerization (ROP) of glycolide (GL) and L,L-lactide (LLA). Biodegradable nanoparticles loaded with the model drug were produced by the o/o method at the first stage of the investigation. Depending on the concentration of the drug in the sample, from 66 to 91% of MT was released over 12 h, according to first-order kinetics. Then, thermosensitive LSs with MT-loaded biodegradable nanoparticles were obtained by a cold method and their mechanical and rheological properties were evaluated. To adjust the thermogelling and mucoadhesive properties for rectal administration, the amounts of major formulation components such as poloxamers (P407, P188), Tween 80, hydroxypropylcellulose (HPC), polyvinylpyrrolidone (PVP), and sodium alginate were optimized. The in vitro release results revealed that more than 80% of the MT was released after 12 h, following also first-order kinetics. It was discovered that the diffusion process was dominant. The drug release profile was mainly governed by the rheological and mechanical properties of the developed formulation. Such a novel, thermosensitive formulation might be an effective alternative to hypertension treatment, particularly for unconscious patients, patients with mental illnesses, geriatric patients, and children.